Shree T, Asnet JM, Kumar R, Mohan T, Shenbagarathai
R., Pharmacophore model of Dengue virus RNA dependent RNA polymerase, Online J Bioinform., 13(1):130-143, 2012.,
The development of a safe and effective therapy for Dengue Fever is a public
health priority at a global level. Novel inhibitors for the viral RNA dependent RNA
polymerase (RdRp), were
identified through Pharmacophore modeling. Using
three known inhibitors for RdRp, ribavirin -5'-
triphosphate, cytidine-5'-triphosphate and triarylpyrazoline, a three point pharmacophore model was generated
using Phase. In order to screen efficient binders of RdRp
from a commercial database (Asinex platinum
collection) containing 150,000 compounds, initial screening was performed using
pharmacophore search and the obtained hits were further screened using docking
protocol. Finally after screening with ADME filters, five compounds with Asinex Id: 71241, 25341, 14859,
5199, 33289 survived. On comparison of free energies of binding of the
obtained hits with the known actives, the novel compounds showed appreciable
free energies of binding (0.095989, 0.095989,
0.095989, 0.820135, -0.01717 kcal/mol respectively). Hence, these
compounds were reported as potential leads to be optimized into potential drugs
after being subjected to in vitro
screening.